Anti-tumour necrosis factor discontinuation in inflammatory bowel disease patients in remission: study protocol of a prospective, multicentre, randomized clinical trial

Background: Patients with inflammatory bowel disease who achieve remission with anti-tumour necrosis factor (anti-TNF) drugs may have treatment withdrawn due to safety concerns and cost considerations, but there is a lack of prospective, controlled data investigating this strategy. The primary study aim is to compare the rates of clinical remission at 1?year in patients who discontinue anti-TNF treatment versus those who continue treatment. Methods: This is an ongoing, prospective, double-blind, multicentre, randomized, placebo-controlled study in patients with Crohn?s disease or ulcerative colitis who have achieved clinical remission for ?6?months with an anti-TNF treatment and an immunosuppressant. Patients are being randomized 1:1 to discontinue anti-TNF therapy or continue therapy. Randomization stratifies patients by the type of inflammatory bowel disease and drug (infliximab versus adalimumab) at study inclusion. The primary endpoint of the study is sustained clinical remission at 1?year. Other endpoints include endoscopic and radiological activity, patient-reported outcomes (quality of life, work productivity), safety and predictive factors for relapse. The required sample size is 194 patients. In addition to the main analysis (discontinuation versus continuation), subanalyses will include stratification by type of inflammatory bowel disease, phenotype and previous treatment. Biological samples will be obtained to identify factors predictive of relapse after treatment withdrawal. Results: Enrolment began in 2016, and the study is expected to end in 2020. Conclusions: This study will contribute prospective, controlled data on outcomes and predictors of relapse in patients with inflammatory bowel disease after withdrawal of anti-TNF agents following achievement of clinical remission. Clinical trial reference number: EudraCT 2015-001410-1

Association between age at disease onset of anti-neutrophil cytoplasmic antibody-associated vasculitis and clinical presentation and short-term outcomes

Objectives: ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- A nd older-onset patients are still incompletely understood. Methods: We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: <65 years or ≥65 years. We adjusted associations for the type of AAV and the type of ANCA (anti-MPO, anti-PR3 or negative). Results: A total of 1338 patients with AAV were included: 66% had disease onset at <65 years of age [female 50%; mean age 48.4 years (s.d. 12.6)] and 34% had disease onset at ≥65 years [female 54%; mean age 73.6 years (s.d. 6)]. ANCA (MPO) positivity was more frequent in the older group (48% vs 27%; P = 0.001). Younger patients had higher rates of musculoskeletal, cutaneous and ENT manifestations compared with older patients. Systemic, neurologic,cardiovascular involvement and worsening renal function were more frequent in the older-onset group. Damage accrual, measured with the Vasculitis Damage Index (VDI), was significantly higher in older patients, 12% of whom had a 6 month VDI ≥5, compared with 7% of younger patients (P = 0.01). Older age was an independent risk factor for early death within 6 months from diagnosis [hazard ratio 2.06 (95% CI 1.07, 3.97); P = 0.03]. Conclusion: Within 6 months of diagnosis of AAV, patients >65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients

A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans – anteaters, sloths, and armadillos – have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with 24 domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, ten anteaters, and six sloths. Our dataset includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data-paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the south of the USA, Mexico, and Caribbean countries at the northern portion of the Neotropics, to its austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n=5,941), and Cyclopes sp. has the fewest (n=240). The armadillo species with the most data is Dasypus novemcinctus (n=11,588), and the least recorded for Calyptophractus retusus (n=33). With regards to sloth species, Bradypus variegatus has the most records (n=962), and Bradypus pygmaeus has the fewest (n=12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other datasets of Neotropical Series which will become available very soon (i.e. Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans dataset

Microbial quality of soil from the Pampa biome in response to different grazing pressures

The aim of this study was to evaluate the impact of different grazing pressures on the activity and diversity of soil bacteria. We performed a long-term experiment in Eldorado do Sul, southern Brazil, that assessed three levels of grazing pressure: high pressure (HP), with 4% herbage allowance (HA), moderate pressure (MP), with 12% HA, and low pressure (LP), with 16% HA. Two reference areas were also assessed, one of never-grazed native vegetation (NG) and another of regenerated vegetation after two years of grazing (RG). Soil samples were evaluated for microbial biomass and enzymatic (β-glucosidase, arylsulfatase and urease) activities. The structure of the bacterial community and the population of diazotrophic bacteria were evaluated by RFLP of the 16S rRNA and nifH genes, respectively. The diversity of diazotrophic bacteria was assessed by partial sequencing of the 16S rDNA gene. The presence of grazing animals increased soil microbial biomass in MP and HP. The structures of the bacterial community and the populations of diazotrophic bacteria were altered by the different grazing managements, with a greater diversity of diazotrophic bacteria in the LP treatment. Based on the characteristics evaluated, the MP treatment was the most appropriate for animal production and conservation of the Pampa biome

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Bloqueo neurolítico del tercer ganglio simpático dorsal en pacientes con síndrome de Raynaud: Una serie de casos

Background: Raynaud's phenomenon, a vascular disorder that is common in the general population, consists of paroxysmal onset distal vasospasm in small cutaneous arteries and arterioles of extremities, usually with little systemic impact. There are anatomical and physiological bases to produce a selective sympathetic block ad using neurolytic agents in the thoracic ganglia T2 and T3 considered synaptic stations that are distributed in the upper limb. Objective: The objective of this work was to determine the efficacy of neurolytic block of the third dorsal ganglion due to Raynaud's syndrome in a series of cases. Material and methods: A review of records of eight cases with Raynaud's phenomenon that presented multifactorial origin were conducted on Clinic of the Pain located in the Unidad Médica de Alta Especialidad, Monterrey Nuevo León, México. Cases: Eight patients from 41 to 72 years old were medically treated for Raynaud's phenomenon using sympathicolysis dorsal third node. Conclusions: Raynaud's phenomenon with a prevalence ranging from 1 to 25% has an increased sympathetic activity. The ischemic pain that is determined by total or partial failure in the oxygen transport to tissues was reduced in these patients by performing a selective sympathicolysis in the thoracic ganglia T2 and T3 considered synaptic stations that are distributed in the upper limb. It was demonstrated in this study that this treatment is selective with less adverse effects to the patients.Introducción: El fenómeno de Raynaud es un trastorno vascular, frecuente en la población general, que consiste en la aparición paroxística de espasmo vascular distal, en pequeñas arterias y arteriolas cutáneas de las extremidades, con escasa repercusión sistémica. Existen bases anatómicas y fisiológicas para producir un bloqueo simpático selectivo utilizando agentes neurolíticos en los ganglios torácicos T2 y T3, considerados estaciones sinápticas que se distribuyen en el miembro superior. Objetivo: Determinar la eficacia del bloqueo neurolítico del tercer ganglio dorsal en el síndrome de Raynaud de una serie de casos. Material y métodos: Se realizó la revisión de expedientes de una serie de ocho casos con fenómeno de Raynaud de causa multifactorial, en la Clínica del Dolor de la Unidad Médica de Alta Especialidad Monterrey; Nuevo León, México. Casos: Ocho casos de 41 a 72 años de edad con fenómeno de Raynaud, tratados médicamente, a los cuales se les realizaron simpaticolisis del tercer ganglio dorsal. Conclusiones: El fenómeno de Raynaud tiene una prevalencia que va del 1 al 25%, en este hay una actividad simpática aumentada por lo que al realizar una simpaticolisis selectiva se logra mejorar el dolor isquémico, el cual está determinado por la insuficiencia total o parcial en el aporte de oxígeno a los tejidos, además de que tenemos bases anatómicas y fisiológicas para limitar el bloqueo a los ganglios T2 y T3, considerados como las estaciones sinápticas que interrumpen los impulsos que se distribuyen en el miembro superior, siendo por tanto más selectivos y con menores efectos adversos para el paciente

Ordovician and Late Paleozoic-Early Mesozoic tectonothermal history of the La Noria area, northern Acatlán Complex, southern Mexico : record of convergence in the Rheic and paleo-Pacific Oceans

The La Noria area lies in the northern part of the polydeformed Acatlán Complex, (southern Mexican Mixteca terrane), and the rocks record the following sequence of events: (i) Early-Middle Ordovician deposition of the volcaniclastic El Epazote and Las Calaveras units; (ii) late Middle Ordovician intrusion of the 467 ± 16 Ma megacrystic, peraluminous, rift-related granitoids; (iii) late Devonian, D₁, greenschist facies deformation; (iv) intrusion of the Los Malpasos leucogranite and associated minor intrusions; (v) Middle Mississippian, D₂, dextral N-S deformation also under greenschist facies metamorphic conditions; and (vi) undated D₃ kink band development. U-Pb LA-ICPMS detrital zircon ages: (a) the El Epazote unit yielded: a mean ²⁰⁶Pb/²³⁸U age from the youngest five concordant ²⁰⁶Pb/²³⁸Pb age of 488 ± 10 Ma, with other age peaks at ca. 506, ca. 1077, and ca. 1779 Ma and a few concordant Neoproterozoic ages: and (b) the Las Calaveras unit yielded a mean ²⁰⁶Pb/²³⁸U age from the sixteen youngest detrital zircons of 466 ± 10 Ma with other population age peaks ca. 1111, and ca. 1753 Ma. These data imply that granitoid intrusion was roughly synchronous with deposition of some of the host rocks. Whereas sources for most of the detrital zircons may be found in either the Acatlán and Oaxacan complexes, Laurentia or Gondwana, a Neoproterozoic source is most likely in Amazonia. The rocks record three low-grade deformational episodes: (i) D₁ produced a weak compositional banding and/or schistosity (S₁) under greenschist facies conditions; (ii) D₂, also occurred under greenschist facies conditions, and developed tight to isoclinal folds (F₂) in S₁ and an axial planar spaced-cleavage (S₂) that is co-planar with S₁; and (iii) D₃ produced reverse and conjugate kink bands (F₃) that deform the S₁/S₂ composite foliation. The leucogranite and related dikes that intrude the complex record only the latter two deformational events. Ca. 330 Ma ⁴⁰Ar/³⁹Ar muscovite plateau ages probably closely post-date the D₂ event. D₁ may be correlated with early Carboniferous deformation elsewhere in the Acatlán Complex. On the other hand, the initial ⁴⁰Ar/³⁹Ar steps at ca. 300, 220 and 172 Ma probably indicate thermal disturbances below 300 °C during the Permo-Carboniferous, Triassic and Jurassic, respectively. Whereas the Ordovician history of the plutons and volcano-sedimentary units coincides with the lifespan of both the Iapetus and Rheic oceans, the Late Paleozoic-Early Mesozoic deformation better reflects closure of the Rheic Ocean and convergence tectonics on the paleo-Pacific margin following the amalgamation of Pangea.19 page(s